Dysregulation of Connexin Expression Plays a Pivotal Role in Psoriasis

Background: Psoriasis, a chronic inflammatory disease affecting 2–3% of the population, is characterised by epidermal hyperplasia, sustained pro-inflammatory immune response and primarily T-cell driven disease. Previous work determined that Connexin26 upregulated in psoriatic tissue. This study extends these findings. Methods: Biopsies spanning plaque (PP) non-involved tissue (PN) were compared to normal controls (NN). RNA was isolated subject real-time PCR determine gene expression profiles, including GJB2/CX26, GJB6/CX30 GJA1/CX43. Protein assessed immunohistochemistry. Keratinocytes fibroblasts used 3D organotypic models. The status cultures via ELISA RnD cytokine arrays presence or absence connexin channel blocker Gap27. Results: dramatically enhanced at both transcriptional translational level PP PN NN (>100x). In contrast, CX43 not affected, but protein post-translationally modified accumulates Fibroblasts from patients had higher index than drove keratinocytes adopt “psoriatic phenotype” 3D-organotypic model. Exposure mediator peptidoglycan, Staphylococcus aureus release, an event protected Conclusion: dysregulation connexin26:43 profile contributes imbalance cellular events. Inhibition signalling reduces events may hold therapeutic benefit.